A detailed understanding of the three-dimensional structure of polyoma virus is a critical step in elucidating the molecular basis for its viral assembly and infection. The objective of this study is to carry out the first detailed structural investigation of an oncogenic virus using single crystal X-ray diffraction methods. The three-dimensional structure of the intact infectious virion and its nucleic-acid-free capsid will be determined. Comparison of these structures will yield an understanding of the organization of the DNA within the protein capsid and may present the first structure of a mini-chromosome. The low-resolution structure will be solved by application of crystallographic molecular-replacement methods. These results will be used to determine the location of heavy atoms in isomorphous derivatives which will be necessary for the high-resolution structure determination.